| Publication type: | Article in scientific journal |
| Type of review: | Peer review (publication) |
| Title: | Suberoylanilide hydroxamic acid : a potential epigenetic therapeutic agent for lung fibrosis? |
| Authors: | Wang, Z. Chen, C. Finger, S. N. Kwajah M.M, S. d/o Jung, M. Schwarz, H. Swanson, N. Lareu, R. R. Raghunath, M. |
| DOI: | 10.1183/09031936.00084808 |
| Published in: | The European Respiratory Journal |
| Volume(Issue): | 34 |
| Issue: | 1 |
| Page(s): | 145 |
| Pages to: | 155 |
| Issue Date: | 2009 |
| Publisher / Ed. Institution: | European Respiratory Society |
| ISSN: | 0903-1936 1399-3003 |
| Language: | English |
| Subject (DDC): | 615: Pharmacology and therapeutics 616: Internal medicine and diseases |
| Abstract: | Pulmonary fibrosis represents a fatal stage of interstitial lung diseases of known and idiopathic aetiology. No effective therapy is currently available. Based on an indication-discovery approach we present novel in vitro evidence that the histone deacetylases inhibitor suberoylanilide hydroxamic acid (SAHA), an FDA approved anti-cancer drug, has antifibrotic and anti-inflammatory potential. Human lung fibroblasts (fetal, adult and idiopathic adult pulmonary fibrosis) were treated with transforming growth factor (TGF)-β1 with or without SAHA. Collagen deposition, α-smooth muscle actin (α-SMA) expression, matrix metalloproteinase (MMP)1 activity, tissue inhibitor of MMP (TIMP)1 production, apoptosis and cell proliferation were assessed. Pro-inflammatory cytokines relevant to pulmonary fibrosis were assayed in SAHA-treated human peripheral blood mononuclear cells (PBMC) and its subpopulations. SAHA abrogated TGF-β1 effects on all the fibroblast lines by preventing their transdifferentiation into α-SMA positive myofibroblasts and increased collagen deposition without inducing apoptosis. However, MMP1 activity and TIMP1 production was modulated without a clear fibrolytic effect. SAHA also inhibited serum-induced proliferation of the fibroblast lines and caused hyperacetylation of α-tubulin and histone. Cytokine secretion was inhibited from PBMC and lymphocytes at nonapoptotic concentrations. Taken together, these data demonstrate combined antifibrotic and anti-inflammatory properties of SAHA, suggesting its therapeutic potential for pulmonary fibrosis. |
| URI: | https://digitalcollection.zhaw.ch/handle/11475/12201 |
| Fulltext version: | Published version |
| License (according to publishing contract): | Licence according to publishing contract |
| Departement: | Life Sciences and Facility Management |
| Organisational Unit: | Institute of Chemistry and Biotechnology (ICBT) |
| Appears in collections: | Publikationen Life Sciences und Facility Management |
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Wang, Z., Chen, C., Finger, S. N., Kwajah M.M, S. d., Jung, M., Schwarz, H., Swanson, N., Lareu, R. R., & Raghunath, M. (2009). Suberoylanilide hydroxamic acid : a potential epigenetic therapeutic agent for lung fibrosis? The European Respiratory Journal, 34(1), 145–155. https://doi.org/10.1183/09031936.00084808
Wang, Z. et al. (2009) ‘Suberoylanilide hydroxamic acid : a potential epigenetic therapeutic agent for lung fibrosis?’, The European Respiratory Journal, 34(1), pp. 145–155. Available at: https://doi.org/10.1183/09031936.00084808.
Z. Wang et al., “Suberoylanilide hydroxamic acid : a potential epigenetic therapeutic agent for lung fibrosis?,” The European Respiratory Journal, vol. 34, no. 1, pp. 145–155, 2009, doi: 10.1183/09031936.00084808.
WANG, Z., C. CHEN, S. N. FINGER, S. d/o KWAJAH M.M, M. JUNG, H. SCHWARZ, N. SWANSON, R. R. LAREU und M. RAGHUNATH, 2009. Suberoylanilide hydroxamic acid : a potential epigenetic therapeutic agent for lung fibrosis? The European Respiratory Journal. 2009. Bd. 34, Nr. 1, S. 145–155. DOI 10.1183/09031936.00084808
Wang, Z., C. Chen, S. N. Finger, S. d/o Kwajah M.M, M. Jung, H. Schwarz, N. Swanson, R. R. Lareu, and M. Raghunath. 2009. “Suberoylanilide Hydroxamic Acid : A Potential Epigenetic Therapeutic Agent for Lung Fibrosis?” The European Respiratory Journal 34 (1): 145–55. https://doi.org/10.1183/09031936.00084808.
Wang, Z., et al. “Suberoylanilide Hydroxamic Acid : A Potential Epigenetic Therapeutic Agent for Lung Fibrosis?” The European Respiratory Journal, vol. 34, no. 1, 2009, pp. 145–55, https://doi.org/10.1183/09031936.00084808.
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